Project activities during the current reporting period have focused predominantly on data analysis, interpretation and manuscript preparation. We are also in the early, planning phases of experiments aimed at documenting the epigenetic consequences of age-related ovarian hormone decline and replacement using immunocytochemical labeling in combination with semi-quantitative microscopy methods in histological sections from the brains of behavioral characterized monkeys. Otherwise, current activities have centered on examining the morphological effects of estrogen deficiency and treatment on synaptic parameters in the hippocampus and dorsolateral prefrontal cortex in young and aged monkeys. Providing a window on the functional significance of the observed effects, all results are evaluated in relation to the cognitive influence of hormone manipulation assessed in the same subjects. Current results are consistent with the emerging view that both the hippocampus and prefrontal cortex regions are sensitive to ovarian hormone regulation in the aged monkey brain. The mechanisms mediating this regulation, and their relationship to the cognitive outcome of aging, appear to be regionally selective.